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Haematology International Journal Research Article 18 min read

The Effects of Ganoderma lucidum Extract on Hematological Malignancy Cell Lines through Different Mechanisms

Mortazavie F, Taheri S and Tamaddon G*
* Corresponding author
ISSN: 2578-501X  10.23880/hij-16000204  Received: September 21, 2022  Published: December 06, 2022
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Keywords
Hematological Malignancies Ganoderma lucidum Fungus Cell Line
Abstract

Hematological malignancies are one of the main reasons of death all over the world. Despite the introduction of various treatments for hematopoietic malignancies, they have a variety of side effects that eventually lead to disease recurrence. Resistance to treatment is the main challenge for patient recovery; therefore, to minimize the toxicity of the commerciallyavailable drugs, some alternatives are needed. Ganoderma lucidum is one of the most well-known medicinal fungus species recommended by Asian physicians and naturopaths to prevent and treat various diseases, including cancers, due to its bioactive and pharmacological components. The present review aimed at collecting recent findings on the molecular mechanism of action of this fungus in different hematological cancer cell lines and investigating how it exerts its anti-cancer activity in these cells.

Introduction

In recent years, people paid considerable attention to natural products, one of their most widely consumed as a folk remedy is Ganoderma lucidum (GL). GL, Reishi or Lingzhi is a basidiomycete, white-rot fungus belonging to the family Ganodermataceae from order Aphyllophorales [1]. It is used in Eastern Asian countries, particularly in traditional Chinese medicine (TCM), for many centuries to prevent and cure diverse human ailments [2], such as nephritis, allergy, bronchitis, asthma, arthritis, hepatitis, hyperglycemia, hypertension, gastric ulcer, hepatopathy, insomnia, and numerous cancers [3]; in addition, it is reported that GL has antioxidant, antiaging, antibacterial, and antiviral activities [4]. Furthermore, G. lucidum is commonly used as an herbal medicine rather than food [5]. Ganoderma lucidum is composed of more than 400 chemical components, including polysaccharides, triterpenoids, amino acids, phenols, sterols, and nucleosides, isolated from the mycelia, spores, and fruiting bodies [6]. Studies indicated that only polysaccharides and triterpenoids, presenting in the natural structure of the fungus, are the most prominently bioactive ingredients and its anti-tumor activity is related to such parts [7].

Polysaccharides, mainly derived from the fruiting bodies of G. lucidum, exert their anti-cancer activity indirectly by increasing host immune responses (Figure 1). Wang Sheng- Yuan, et al. observed that polysaccharides can stimulate the production of cytotoxic T- (CTL) and B-lymphocytes, natural killer (NK) cells, and macrophages, and ultimately increase the secretion of cytokines, such as interleukin (IL)-1B, IL- 6, tumor necrosis factor (TNF), and interferon-ϒ (IFN-ϒ) [8]. Moreover, evidence from previous studies suggests that G. lucidum polysaccharides (GLPs) exert their anticancer activities through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic, and anti-angiogenic effects [9, 10].

Figure 1: Structure of Reishei polysaccharide.
Click to enlarge
Figure 1: Structure of Reishei polysaccharide.

G. lucidum triterpenoids (GLTs), a subtype of trepan, consist of six isoprene units that may form linear or folded chains to form a ring-like structure. Triterpenes, mostly extracted from the spores of G. lucidum, play a pivotal role in directly inhibiting cancer cells. There are different types of triterpenes with various cytotoxic effects (Figure 2). Evidence suggests that some types of triterpenes have potent toxic effects at low concentrations on different human cancerous cell lines [11, 12, 13]. Ganoderic acid T is the most profuse known triterpene of G. lucidum with extraordinary anti-cancer activity in both in-vitro and in-vivo. In a study by Tang Wen, Ganoderic acid T from G. lucidum mycelia induced mitochondria-mediated apoptosis in lung cancer cells [14].

Ganoderic acid an enhanced induction of cisplatin cell death by increasing the sensitivity of HepG2 cells to cisplatin mainly via the signaling transducer and activator of transcription 3 suppression in a study by Yao Xiangyang [15]. Chen Liwu reported that ganoderic acid C2 led to aldose reductase inhibition in the HepG2 cell line [16]. Ganoderic acid D (GAD) is one of the major components in GLTs; in a recent report by Yue et al., it was observed that GAD causes G2/M cell cycle arrest and induces apoptosis in Hela human cervical cancer cells [17]. Xia Junbo showed that ganoderic acid DM induces the autophagic apoptosis in non-small lung cancer cells by suppressing the PI3K/AKT/mTOR activity [18].

Figure 2: The main structure of Ganoderma lucidum triterpenoid and its different types.
Click to enlarge
Figure 2: The main structure of Ganoderma lucidum triterpenoid and its different types.

Currently available data show that Lingzhi induces apoptosis and suppresses the growth and proliferation of cancerous cells through multiple molecular mechanisms; therefore, it can be concluded that this mushrroom has a potent cytotoxicity against different cancers, including leukemia. The current study aimed at investigating the mechanisms of cancer cell killing by GLPs and GLTs in hematopoietic cell lines.

Effect of Ganoderma lucidum on the THP-1 Cell Line (Acute Monocytic Leukemia)

A study investigating the effect of GLPs extract on acute monocytic leukemia concluded that GLP was capable of inducing death receptor ligands such as TNF-alpha and TRAIL to trigger signaling followed by oligomerization of death receptors, utilization of adaptor proteins, and stimulation of caspase cascade. Therefore, induction of apoptosis via death receptors after treating THP-1 cells with G. lucidum extract plays a pivotal role in the research [19].

Chan Wing Keung, et al. in a similar study, elucidated that GLPs have an immunomodulating role in THP-1 cells. GLPs possess the potential to induce the differentiation of THP-1 into DCs in the presence of cytokines, including IL-4 and GM- CSF; this event is associated with significant upregulation of antigen expression and costimulation molecules, and it should be noted that GLP products possibly sorely limit T-cell lymphocytes through downregulation [P2] of IL-10 production. it is observed that GLPs induce the differentiation of autologous blast cells into dendritic cells and decrease tumor cells burden [20].

Watanabe Kenji, et al. investigated the effect of triterpene-rich extract from G. lucidum AF on THP- 1 monocytic cells. Notably, accumulated data show that G. lucidum AF induces TNF-α production in both lipopolysaccharide-treated and non-treated monocytic THP- 1 cells and has a synergistic effect on THP1 cells treated with lipopolysaccharides (LPSs). Evidence suggested that G. lucidum AF increased phosphorylation of p38 MAPK induced by LPSs, which suppressed TNF-α production and decreased phosphorylation of c-Jun N-terminal kinase (JNK) MAPK, induced by LPSs that enhanced TNF-α production. Accordingly, G. lucidum isolated from triterpenes possibly stimulated immune responses, induced by LPSs via the modulation of p38 and JNK MAPKs activation in the THP-1 cell line [21].

Based on previous data published by the journal of the Evidence-Based Complementary and Alternative Medicine, exposure to GLPs strongly induces macrophage differentiation in THP-1 cell line via activation of caspase and p53. It is known that therapeutic differentiation is an important approach to the treatment of hematological cancers, including leukemia, which helps to eliminate the growth and proliferation of cancerous cells. As confirmed by various molecular experiments, caspase activation and up-regulation of p53 and p21 contribute to the macrophage differentiation process. The current study suggested that the treatment of human leukemia THP-1 cell enhances the expression of p53 and p21 and also the activation of the caspase pathway, which facilitate cellular differentiation and elevate the expression of macrophage differentiation markers in such leukemia cells [22].

Emerging evidence demonstrated that treatment with active lipids isolated from G. lucidum spores can drastically induce apoptosis in the THP-1 cell line through the suppression of ERK1/2 and AKT and activation of JNK1/2. Moreover, treatment of THP-1 cells with active lipids from G. lucidum led to upregulation of caspase 3, 8, and 9 in a dose- and time-dependent manner, which mediated apoptotic induction. Hence, according to reports, MAPK and PI3K signaling pathways play the most prominent role in the modulation of cell death by active lipids from G. lucidum in THP-1 monocytic cells [23].

Rathor Richa, et al. studied the impact of hydro-ethanolic extract of G. lucidum (HEGL) on inflammatory cytokines,and NF-kB activity and also its antioxidant property in monocytic THP-1 cells. Results of their study indicated that HEGL strongly suppressed the production of inflammatory mediators, including TNF-α, IFN-y, IL-1β, NO, and NF-kB in LPS-stimulated THP-1 cells; hence, this information proved the immunomodulatory activity of HEGL in LPS-treated THP- 1 cells [24].

The Effect of Ganoderma lucidum on Ramos and Daudi Cell Lines (Burkitt’s Lymphoma)

Recently, to determine the magnitude of apoptotic cell death, Ganoderic acid A (GAA) treatment was also examined on Ramos and Daudi cells; the accumulated data in this regard illustrated that the GLT had profound apoptotic characteristics through an intrinsic pathway correlated with mitochondrial dysfunction in such cells. The results of studies indicated that GAA treatment disturbed the mitochondrial membrane potential followed by enhanced cytochrome c cytosolic levels and cleavage caspases 3, 8, and 9. In addition, pro-apoptotic protein BIM and BAX up-regulated by GLT and downregulated anti-apoptotic protein bcl-2; hence, GAA in a dose- and time-dependent manner inhibited the cell proliferation and induced apoptosis [25].

In another study, G. lucidum extract was examined on a panel of 26 human cancer cell lines, including Daudi and Ramos, and reported its antitumor activity. This preliminary screening study displayed that the extract from G. lucidum induced apoptosis in these cell lines, but unfortunately, the underlying mechanism of the anti-cancer activity remained unknown in Daudi and Ramos cell lines (Table 1) [26].

Type of
G.lucidum
component		Type of
study		Type of cell
line		ResultsPotential
mechanism of
action		IC50Incuba-
tion time		Reference
Polysaccharide
fraction of
G.lucidum		LaboratoryAcute
monocytic
leukemia
(FAB M5)		Induce
apoptosis in
THP-1 cell line		Induces death
receptor ligands
such as TNF-a and
TRAIL and activation
of caspase cascades		30 μg/ml48 hCheng Kun-
Chieh, et al.
[19]
Polysaccharide
fraction of
G.lucidum		LaboratoryAcute
monocytic
leukemia
(FAB M5)		Reduce cancer
cell burden in
THP-1 cell line		Increase the
cell proliferation
and induce
differentiation of
THP-1 into DC and
down-regulating
of T-lymphocyte
through by decrease
IL-10		100 μg/
ml		72 hChan Wing
Keung, et
al. [20]
Triterpenes
rich-extract of
G.lucidum AF		LaboratoryAcute
monocytic
leukemia
(FAB M5)		Induce TNFa
production in
THP-1 cell line		Increase
LPS-induced
phosphorylation
of p38 MAPK and
inhibit LPS-induced
phosphorylation of
JNK MAPK		50 μg/ml4 hWatanabe
Kenji, et al.
[21]
Polysaccharide
fraction of
G.lucidum		LaboratoryAcute
monocytic
leukemia
(FAB M5)		Induce
macrophage
differentiation
in THP-1 cell
line		activate caspase
cascade and
up-regulating
of p53 and p21
and elevated
of Macrophage
differentiation
markers		30μg/ml4 hHsu Jia-Wei,
et al. [22]
Active lipid
of G.lucidum
spores		LaboratoryAcute
monocytic
leukemia
(FAB M5)		Induce
apoptosis in
THP-1 cell line		Inhibit ERK1/2, AKT,
activate JNK1/2
signaling pathway
and up-regulating of
caspase 3, 8 and 9		1 mg/ml48 hWang Jia-
He, et al.
[23]
Hydro-
ethanolic
extract of
G.lucidum
(HEGL)		LaboratoryAcute
monocytic
leukemia
(FAB M5)		Possesses
anti-oxidant
property in
LPS-treated
THP-1 cells		Inhibit production of
TNF-α, IFN-y, IL-1β,
NO and NF-kB		100
μg/ml		24 hRathor
Richa, et al.
[24]
Triterpenoid
fraction of
G.lucidum		LaboratoryBurkitt’s
lymphoma
(Ramos.
Daudi)		Induce
apoptosis in
Ramos and
Daudi cell lines		Enhance activation
of caspase 3, 8 and
9, up-regulating
of pro-apoptotic
proteins BAX. BIM
and down-regulating
of anti-apoptotic
proteins bcl-2		18.5-22
μM		24 hRadwan
Faial FY, et
al. [25]
Triterpenoid
fraction of
G.lucidum		LaboratoryHuman acute
lymphoblastic
leukemia
(FAM M2)		Induce
apoptosis in
HL-60 cell line		Up-regulating of bcl-
2, BAX translocation,
mitochondrial
cytochrome c
release and caspase
3 activation		210 μg/
ml		6,24 hKim Kug
Chan, et al.
[27]
Triterpenoid
fraction of
G.lucidum		LaboratoryHuman acute
lymphoblastic
leukemia
(FAM M2)		Induce
apoptosis in
HL-60 cell line		Inhibit CDK1
phosphorylation
and the
dephosphyraltion of
pRB and induce G1
phase arrest		150 μg/
ml		48hHsu Jia-Wei,
et al. [22]
Triterpenoid
fraction of
G.lucidum		LaboratoryHuman acute
lymphoblastic
leukemia
(FAM M2)		Induce
apoptosis in
HL-60 cell line		Inhibit CDK1
phosphorylation
and the
dephosphyraltion of
pRB and induce G1
phase arrest		150 μg/
ml		48hKim Kug
Chan, et al.
[28]
G.lucidum
extract		LaboratoryHuman acute
lymphoblastic
leukemia
(FAM M2)		Reduce the
proliferation
activity in HL-
60 cell line		Decrease
mitochondrial
membrane potential
and decrease G1
phase progression		136.3
μg/ml		48hLiu Yue
Wei, et al.
[29]
ergosta‐7,22‐
diene‐2β,3α,9α‐
triol (EGDT)		LaboratoryHuman acute
lymphoblastic
leukemia
(FAM M2)		Induce
apoptosis in
HL-60 cell line		Increase DNA
fragmentation and
activation of caspase
3		12.7 μg/
ml		24hLee Mi
Kyoung, et
al. [30]
Polysaccharide
fraction of
G.lucidum		LaboratoryHuman acute
lymphoblastic
leukemia
(FAM M2)		Induce
apoptosis in
HL-60 cell line		Activate p38 and
JNK MAPK pathway
and regulating of
their downstream
genes and proteins		200-800
μg/ml		20,48,72hYang
Gouhua, et
al. [31]
Polysaccharide
fraction of
G.lucidum		LaboratoryHuman
chronic
myelocytic
leukemia		Reduce
resistance to
Adriamycin in
K562 cell line		Regulating of
MDR-1 and MRP-1
transcription factors		50 mg/L44hLi Wei
dong, et al.
[32]
Ganoderma
extract and
spores oil		LaboratoryHuman
chronic
myelocytic
leukemia		Blocking the
cell cycle in
K562 cell line		inhibit the
topoisomerase I
and II activity and
decrease of cyclin
D1		0.39 mg/
ml		24hChen Chun,
et al. [33]
Fruiting bodies
of G.lucidum		LaboratoryHuman acute
promyelocytic
leukemia
(FAB M3)		Induce
apoptosis in
NB4 cell line		Reduce of p53, AKT
and ERK levels		60 μg/ml19hCalvino
Eva, et al.
[34]
Ergosterol
peroxide (EP)		LaboratoryHuman
multiple
myeloma		anti-tumor
activity in
U266 cell line		Inhibit STAT3
signaling pathway		25
μM		24hRhee Yun
Hee, et al.
[35]
Fruiting bodies
of G.lucidum		LaboratoryPre-B acute
lymphoblastic
leukemia		Causes
apoptosis in
Blin1 cell line		No cell cycle arrest
was observed in
G2/M phase		38 μg/ml96hMuller
Claudia I, et
al. [26]
Fruiting bodies
of G.lucidum		LaboratoryNon-T,
non-B acute
lymphoblastic
leukemia		Causes
apoptosis in
NALM-6 cell
line		Arrest the cell cycle
in G2/M phase		30 μg/ml96hMuller
Claudia I, et
al. [26]
Triterpenoid
fraction of
G.lucidum		LaboratoryNon-T,
non-B acute
lymphoblastic
leukemia		Induce
apoptosis in
NALM-6 cell
line		Regulating of
caspase activity and
BAX , BCL-2 and
APAF1 expression		40
mM		24hRadwan
Faisal FY, et
al. [25]
Triterpenoid
fraction of
G.lucidum		LaboratoryNon-T,
non-B acute
lymphoblastic
leukemia		Induce
apoptosis in
NALM-6 cell
line		Reduce the
expression of miR-
17-5p and miR-
181b and induce
apoptosis		140 μg/
ml		48hMortazavie
Faezeh, et
al. [36]
Diffuse
histiocytic
leukemia (
monocytic
leukemia cell)		LaboratoryCauses
apoptosis in
U937 cell line		Increase
protein
expression of
p21WAFI and
p27 KIPI and
No cell cycle
arrest was
observed in
G2/M phase		63 μg/ml96 hMuller
Claudia I, et
al. [26]
Fruiting bodies
of G.lucidum		LaboratoryMultiple
myeloma		Causes
apoptosis in
RPMI8226 cell
line		Arrest the cell cycle
in G2/M phase		40 μg/ml96 hMuller
Claudia I, et
al. [26]

Table 1: Selected laboratory and pre-clinical studies of G.lucidum component.

Effect of Ganoderma lucidum on the HL-60 Cell Line (Acute Myeloblastic Leukemia)

Kug Chieh Chan Kim, et al. investigated the effect of G. lucidum extract on human promyelocytic leukemia cells (HL-60) and found that this fungus alone or in combination with Duchesnea chrysatha (GDE) increased the permeability of the mitochondrial membrane and induced the apoptosis in the HL60 cell line. Based on these data, the reduction in mitochondrial membrane potential was probably related to cytochrome c release, Bax expression, caspase3 activation, and BCL-2 regulation [27].

A study published in 2008 in Cancer Letters journal indicated that the simultaneous use of the combination of GL and DL with radiotherapy strongly induced mitochondrial damage and apoptosis. This combination triggered apoptosis through a mitochondrial-intrinsic pathway by increasing the activity of proapoptotic proteins, such as Bax, Smac/DIABLO, and caspase-3. Also, after exposure to Gl and DC, the HL-60 cells became more sensitive to γ-irradiation by changing the level and duration of the cell cycle arrest in G1 and G2/M phases through inhibition of pRB and CDK1/cyclin B1 checkpoint proteins phosphorylation, respectively [28].

It is recently found that ethanolic extracts of G. lucidum have anti-proliferative activity on acute promyelocytic leukemia cells. After treatment with Ganoderma extract, the HL-60 cells exhibit time-dependent changes in the cell cycle. The cell cycle was significantly arrested at the G2/ M transition [29].

It is reported that, among the chemical compounds in the fruit body of G. lucidum, EGDT (ergosta‐7, 22‐diene‐2β, 3α, 9α‐triol) has the highest cytotoxic effect on HL-60 cells. EGDT enhanced cleavage of procaspase-3, procaspase‐3, poly (ADP‐ ribose) polymerase (PARP), and DNA fragmentation that are associated with apoptosis process; though the apoptotic activity of EGDT was a dose‐dependent manner [30].

An investigation on the polysaccharide obtained from G. lucidum indicated its anti-cancer effects, both directly through signaling pathways and indirectly by regulating the immune system. These findings illustrated that phosphorylated MEK and ERK1/2 in the cells treated with GLP remarkably reduced in a dose- and time-dependent manner. GLP blocked the ERK/MAPK signaling pathway. On the other hand, the levels of IL-2, IL-6, IL-12, and TNF-a in the serum of the nude mice xenograft model were measured, and the results indicated that GLP increased their levels; thus, GLP can indirectly regulate the immune system [31].

The Effect of Ganoderma lucidum on The K562 Cell Line (Erythroid Chronic Myeloid Leukemia)

One of the reasons for cancer treatment failure is multidrug resistance (MDR). Overexpression of MDR1 (multidrug resistance), MRP1 (MDR-associated protein), and P-gp (P-glycoprotein) is observed in drug-resistance cell lines. In a previous study, in order to find a drug with higher MDR activity [P3] and lower toxicity, the effect of polysaccharides (Gl-PS) extracted from the fruit body of G. lucidum on the multidrug cell line K562/ADM was investigated. The findings showed that the expression of MRP1 and MDR1 decreased in exposure to GL-PS. Although Gl-PS had less toxic effects on normal cells, it reversed the resistance of K562/ADM to ADM [32].

A study on the effects of G. lucidum extract and spore oil on the molecular mechanisms, underlying their effects on the K562 cell line, specified that its anti-growth activity is due to blocking cell cycle at the transition between the G1 and S phases, decrease in cyclin D1 levels, and topoisomerase suppression. Topoisomerase enzyme is involved in the regulation of DNA supercoiling. Also, topoisomerase overexpression is observed in some hematologic malignancies. The suppression of topoisomerase I and II activities destructs dividing cancer cells in a dose dependent manner [33].

Effect of Ganoderma lucidum on NB4 Cell Line (Promyelocytic Leukemia)

Chen Chun, et al. discovered that NB4 human leukemia cells underwent intracellular changes after treatment with G. lucidum aqueous extract. Decrease in cell viability by inducing apoptosis, reduction of p53, Bcl-2 level, Erk, and pErk2 proteins synthesis, and increase in the Bax level were all due to the effect of Ganoderma on NB4 [34].

Effect of Ganoderma lucidum on U266 Cell Line (Multiple Myeloma)

One of the components of G. lucidum is ergosterol peroxide (EP), which has an anti-tumor effect on the U266 multiple myeloma cells. According to studies, the antitumor mechanism of EP on U266 is associated with its inhibitory effects on the signaling pathways of stat3. The stat3 is a cytoplasmic transcription factor involved in the regulation of genes encoding apoptosis inhibitors, such as BCL-xL, and BCL-2. EP remarkably suppresses JAK2 and Src activation, stat3 phosphorylation, and stat3 DNA-binding activity. It also induces SHP-1 protein expression, playing a pivotal role in inhibiting stat3 phosphorylation; all the processes were in a time- and dose-dependent manner [35].

Effect of Ganoderma lucidum on the Nalm-6 Cell Line (Non-T, Non-B Acute Lymphoblastic Leukemia)

Muller assessed the cytotoxic potential of G. lucidum extract against human cancer cell lines and reported that G. lucidum effectively inhibited the proliferation of Nalm-6 cells, which were one of the cell lines with the greatest sensitivity to this fungus. As explained, the fungal extract has an antitumor proliferation activity via both apoptotic pathway and cell cycle arrest on the G2/M phase, but unfortunately, information in the current study does not elucidate the exact mechanism by which the GLE induces apoptosis [26].

A study on Nalm-6 cells proved that Ganodric acid A reduces cell viability. Also, according to the findings, increased caspase expression and activity 3, 8, 9, and pro-apoptotic BIM, BAX proteins, decreased BCL-2 protein, high levels of APAF-1, and cytochrome c consequently led to apoptotic cell death in pre-B acute lymphocytic leukemia [25].

In an article published in 2022, the anticancer activity of Ganoderic acid an extract was evaluated on changes in the expression of miR-17-5p and miR-181b and the induction of apoptosis in the Nalam 6 cell line. According to the results of this study, Ganoderic acid A has the ability to greatly reduce the expression of miR-17-5p and miR-81b and induce cell apoptosis in the Nalm-6 leukemic cell line [36].

The effect of Ganoderma lucidum on the Blin-1 (pre-B acute lymphoblastic leukemia), Jurkat (T-cell acute lymphoblastic leukemia), U937 (diffuse histocytic leukemia), SUDHL6 (diffuse large B-cell lymphoma), and the ARH77 and RPMI8226 cell lines (multiple myeloma). A paucity of laboratory and pre-clinical studies evaluated anti-tumor activity of Reishi mushroom on the human cell lines, such as Blin-1, Jurkat, U937, AHR77, RPMI8226, and SUDHL6; the findings of their field suggested that G. lucidum extract induced apoptosis in these cell lines, but the results were incomplete from certain aspects; hence, further research is needed until exact mechanism of action is fully elucidated. Based on the available and relevant information, after the exposure of U937 cell line to different concentrations of G. lucidum extract for 48 and 72hours, the expression of apoptosis-related proteins, including p21 and p27, increased; even though there was no G2/M arrest after treatment with G. lucidum in the U937 cells in; additionally, it was observed that G. lucidum extract lightly enhanced cells in the RPML8226 in the G2/M phase [26].

Conclusion

Ganoderma lucidum is one of the famous medicinal fungi regarded as a promising anti-cancer immunotherapy agent due to its pharmacological properties and minimum side effects; since G. lucidum could be a drug of choice for the development of a novel class of anti-cancer drug. The present review evaluated the recent findings on the exact mechanism pathway in hematological cancer cell lines. Until now, extensive studies are performed on the anti-cancer activity of this magic mushroom; nevertheless, molecular and immune-supportive mechanisms in cancer cell lines are not fully elucidated accordingly. There is a scope for prospective research, especially since the mechanisms underlying immune modulation should be explored in detail, which can prove the efficiency and safety of this fungus; perhaps further studies provide new insight into the potential therapeutic applications of G. lucidum to combat cancer.

Acknowledgments

Authors extend their gratitude to the staff of the Diagnostic Laboratory Sciences and Technology Research Center of the School of Paramedical Sciences, Shiraz University of Medical Sciences, and Shiraz, Iran.

Conflict of Interest Statement

The authors declared no conflicts of interest. It was a review study and informed consent or ethical approval was not applicable.

Funding

There was no funding for the study. Table selected laboratory and pre-clinical studies of G. lucidum component.

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@article{mortazavie2022,
  title   = {The Effects of Ganoderma lucidum Extract on Hematological
Malignancy Cell Lines through Different Mechanisms},
  author  = {Mortazavie F, Taheri S and Tamaddon G},
  journal = {Haematology International Journal},
  year    = {2022},
  volume  = {6},
  number  = {2},
  doi     = {10.23880/hij-16000204}
}
Mortazavie F, Taheri S and Tamaddon G (2022). The Effects of Ganoderma lucidum Extract on Hematological
Malignancy Cell Lines through Different Mechanisms. Haematology International Journal, 6(2). https://doi.org/10.23880/hij-16000204
TY  - JOUR
TI  - The Effects of Ganoderma lucidum Extract on Hematological
Malignancy Cell Lines through Different Mechanisms
AU  - Mortazavie F, Taheri S and Tamaddon G
JO  - Haematology International Journal
PY  - 2022
VL  - 6
IS  - 2
DO  - 10.23880/hij-16000204
ER  -